Increasing evidence suggests that vasopressin (VP) may play a role in the development of numerous forms of experimental hypertension, including the DOCA/salt model. Of great importance is the finding that VP-deficient Brattleboro rats (DI rats) fail to develop hypertension with DOCA/salt but do so when replaced with VP. Little is known of the mechanism of action of VP in hypertension. The present research plan proposes to define the role of VP in DOCA/salt hypertension and identify its mechanism(s) of action. VP may act as a direct vasoconstrictor. This will be tested by assessing arterial pressure (AP) and regional (hindlimb, mesenteric and renal) flow responses to VP in conscious DOCA/salt treated rats instrumented with chronic catheters and miniaturized pulsed Doppler flow probes at various stages of hypertension. VP may act indirectly as a modulator of the responsiveness of vascular smooth muscle to other vasoconstrictors. This will be tested by assessing vascular reactivity in isolated, perfused vascular beds. Finally, VP may act indirectly by modulating the function of brain centers involved in AP regulation. This will be tested by 1) determining the effects of VP levels on baroreceptor sensitivity, 2) determining effects of stimulation and ablation of VP-synthetic nuclei (paraventricular and supraoptic) on AP, regional hemodynamics and baroreceptor function, 3) comparing effects of stimulation of central cardiovascular centers in DI rats devoid of VP with effects obtained in normal rats and 4) determining the effects of central infusions of VP on AP, regional hemodynamics and baroreflex sensitivity. The results of these experiments should provide fundamental information on the role of VP in normal cardiovascular regulation as well as in the pathogenesis of hypertension.